Inhibitory effects of angiotensin-(1–7) on the nerve stimulation-induced release of norepinephrine and neuropeptide Y from the mesenteric arterial bed

Abstract

Neuropeptide Y (NPY) is a cotransmitter with norepinephrine (NE) and ATP in sympathetic nerves. There is evidence for increased activity of the sympathetic nervous system and the renin-angiotensin system (RAS), as well as a role for NPY in the development of hypertension in experimental animal models and in humans. Angiotensin II (ANG II) is known to facilitate sympathetic neurotransmission, an effect greater in spontaneously hypertensive rats (SHR) than normotensive Wistar-Kyoto (WKY) rats. A newly discovered product of the RAS is angiotensin-(1-7) [ANG-(1-7)]. There is evidence suggesting that ANG-(1-7) opposes the actions of ANG II, resulting in hypotensive effects. The objective of this study was to investigate the role of ANG-(1-7) on the nerve-stimulated overflow of NE and NPY from the mesenteric arterial bed of SHR and the mechanisms involved in mediating any effects produced. ANG-(1-7) (0.001, 0.01, 0.1 microM) decreased nerve-stimulated NE and NPY overflow, as well as perfusion pressure in preparations obtained from SHR. This effect was greater in preparations of SHR than WKY controls. In addition, ANG-(1-7) decreased NE overflow to a greater extent than NPY overflow. Administration of the Mas receptor antagonist, D-Ala(7) ANG-(1-7), attenuated the decrease in both NE and NPY overflow due to ANG-(1-7) administration. However, the angiotensin type 2 receptor antagonist, PD-123391, attenuated the effect of ANG-(1-7) on NE overflow without affecting the decrease in NPY overflow. Moreover, in the presence of N(G)-nitro-L-arginine methyl ester, ANG-(1-7) decreased NPY overflow, but not NE overflow. ANG-(1-7) decreases the nerve-stimulated overflow of NE and NPY in preparations of SHR, whereas ANG II enhances it. Therefore, ANG-(1-7) may counteract the effects of ANG II by acting on ANG type 2 and Mas receptors.

Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options

“…When all HUT(ϩ) subgroups were analyzed collectively, an increase in hormone secretion from the supine position to HUT included AVP, NE, Epi, renin, and ANG II. Although ANG-(1-7) has been reported to influence AVP and NE release and baroreflex function in animal studies (7,17,44,57), there were no differences in ANG-(1-7) between groups. A negative relationship was observed between ANG-(1-7) and NE, consistent with evidence of a neuromodulatory action of ANG-(1-7) on the release of NE (7, 17, 48, 57).…”

Neuronal and non-neuronal modulation of sympathetic neurovascular transmission

“…This increase in O 2 − will decrease NO availability and further augment norepinephrine levels in the neurovascular junction that will then blunt NPY release via negative feedback mechanisms. A further example is the observation that, in addition to direct pre-junctional inhibitory effects on norepinephrine and NPY overflow, the angiotensin metabolite, Ang 1–7 decreases norepinephrine overflow from the mesenteric bed in a NOS dependent manner (Byku et al , 2010). …”

Advances in the Renin Angiotensin System

“…Findings involving the application of A-779 to evaluate Ang-(1–7) actions appear to confirm the involvement of the mas-R (Santos et al, 1994). Using this antagonist, studies have reported that A-779 prevents the inhibitory actions of Ang-(1–7) on nerve stimulation-mediated release of norepinephrine and neuropeptide Y (Byku et al, 2010), myocardial contractility (Castro-Chaves et al, 2009), and stimulation of cardiac Akt phosphorylation and Ang II-stimulated ERK1/2 and Rho kinase phosphorylation (Giani et al, 2008). The use of mice with genetic deletion of the mas-R has affirmed conclusions derived from pharmacological blockade of Ang-(1–7) (Santos et al, 2003, 2006).…”